Virtual screening and antiepileptic activity evaluation of CaMK Ⅱ modulatory components from the herb pair,Polygala tenuifolia and Zizyphus jujuba
Objective To screen the potential active calcium/calmodulin-dependent protein kinase Ⅱ(CaMK Ⅱ)modulatory components from Poly gala tenuifolia and Zizyphus jujuba with virtual screening and pharmacological evaluation methods.Methods Virtual screening was possessed based on the pharmacophore methods.Bycollecting the information of compounds with CaMK Ⅱmodulatory activity reported in the literature,HipHop pharmacophore model based on CaMK Ⅱ ligands was established,and the components from P.tenuifolia and Z.jujuba was collected to match the pharmacophore.Subsequently,the interactions between matched small molecule compounds and CaMK Ⅱ target(PDB ID:2V7O)were analyzed through molecular docking methods.Pentylenetetrazol(PTZ)-induced seizure mice model was established to evaluate the antiepileptic effect of the screened monomers.Tenuifoliside A(39)was selected to evaluate its modulatory effects of CaMK Ⅱ in the antiepileptic model.Results Through literature search,an in-house compound library with 109 kinds of chemical constituents from P.tenuifolia and Z.jujuba was established,then the optimal pharmacophore 03 was selected through test set verification for virtual screening of the compound library.Six kinds of potential CaMK Ⅱ modulatory constituents were obtained,and the interaction of the compounds with CaMK Ⅱwas analyzed by docking studies.Compound 39 was proved to prolong the latent time of PTZ-induced seizures,improve anxiety and depressive-like behavior induced by PTZ,promote the amount of Nissl body,and increase the expression level of CaMK Ⅱ.The number of CaMK Ⅱ immuno-positive cells in CA1,CA3 of hippocampus and temporal cortex regions was promoted as well with the regulation of the level of nAChR4.Conclusion The results showed that it was reasonable to investigate the CaMK Ⅱ modulatory components of P.tenuifolia and Z.jujuba based on virtual screening and activity evaluation.
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